Biomedical Sciences Research Centre "Alexander Fleming," Vari, Greece.
Muhimbili University of Health and Allied Sciences, School of Medicine, Dar es Salaam, Tanzania.
Gastroenterology. 2017 Apr;152(5):964-979. doi: 10.1053/j.gastro.2016.11.049. Epub 2017 Jan 20.
Mesenchymal cells in the intestine comprise a variety of cell types of diverse origins, functions, and molecular markers. They provide mechanical and structural support and have important functions during intestinal organogenesis, morphogenesis, and homeostasis. Recent studies of the human transcriptome have revealed their importance in the development of colorectal cancer, and studies from animal models have provided evidence for their roles in the pathogenesis of colitis-associated cancer and sporadic colorectal cancer. Mesenchymal cells in tumors, called cancer-associated fibroblasts, arise via activation of resident mesenchymal cell populations and the recruitment of bone marrow-derived mesenchymal stem cells and fibrocytes. Cancer-associated fibroblasts have a variety of activities that promote colon tumor development and progression; these include regulation of intestinal inflammation, epithelial proliferation, stem cell maintenance, angiogenesis, extracellular matrix remodeling, and metastasis. We review the intestinal mesenchymal cell-specific pathways that regulate these processes, with a focus on their roles in mediating interactions between inflammation and carcinogenesis. We also discuss how increasing our understanding of intestinal mesenchymal cell biology and function could lead to new strategies to identify and treat colitis-associated cancers.
肠中的间质细胞包含多种不同来源、功能和分子标记的细胞类型。它们在肠道器官发生、形态发生和稳态中提供机械和结构支持，并具有重要功能。人类转录组的最新研究揭示了它们在结直肠癌发展中的重要性，动物模型的研究为它们在结肠炎相关癌症和散发性结直肠癌发病机制中的作用提供了证据。肿瘤中的间质细胞，称为癌相关成纤维细胞，通过激活固有间质细胞群以及招募骨髓来源的间充质干细胞和纤维细胞而产生。癌相关成纤维细胞具有多种促进结肠肿瘤发生和进展的活性；这些包括调节肠道炎症、上皮细胞增殖、干细胞维持、血管生成、细胞外基质重塑和转移。我们回顾了调节这些过程的肠间质细胞特异性途径，重点讨论了它们在介导炎症和致癌作用之间相互作用中的作用。我们还讨论了如何加深对肠间质细胞生物学和功能的理解，从而为识别和治疗结肠炎相关癌症提供新策略。
